The total enatioselective synthesis of the natural products YW3548 and YW3699 isolated from the fungus Paecilomyces inflatus and Codinaea simplex is planned. Both natural products have been shown to be species-specific inhibitors of glycosylphosphatidylinositol (GPI) biosynthesis.The key step involves a Ni(II) / Cr(II) -mediated cyclization between a vinyl iodide and a ketone for formation of the eight-membered ring. This proposed strategy represents a new application of this reaction. In addition, several new synthetic methodologies will be developed during the course of the synthesis. The resulting work will be useful in the preparation of analogs for the purpose of probing GPI synthesis in eukaryotic systems with potential clinical applications.